Lead poisoning appears to damage the developing central nervous system primarily through its effects on the development of the microvasculature. Previous work suggests that there are direct toxic effects on developing neurons but that the major alterations are secondary to vascular injury. It is the aim of the proposed research to study the development of the microvasculature of the neonatal rat cerebellum with special emphasis on cellular mechanisms of injury and the relationship, if any, to angioblasts. The animal model to be used in this investigation involves feeding defined quantities of lead to neonatal rats with an esophageal catheter. The cerebellar vermis will be the area of the brain studied. It is developmentally characterized in normal and lead poisoned animals and is markedly altered by lead intoxication. Standard electron microscopic methods employing serial sections and the Golgi technique will be used to characterize the ultrastructure of angioblasts in lead poisoned and control rats. The sequential changes in the vascular pattern will be determined in both lead poisoned and control rats using colloidal carbon and horseradish peroxidase as vessel contrast materials. Changes in the "blood-brain barrier" function of the cerebellar endothelium will be studied using horseradish peroxidase as an ultrastructual tracer. The permeability changes of the segments of the microcirculation (arteriole, arteriolar portion of capillary, mid capillary, venular portion of capillary, venule) will be individually characterized. Preliminary work with this tracer has shown a marked increase in permeability at an early stage of lead poisoning. Morphologic information of angioblast structure will be used to determine the relationship of new vessel formation to the increase vascular permeability of lead poisoning.